Access to Highly Enantioenriched Donepezil-like 1,4-Dihydropyridines as Promising Anti-Alzheimer Prodrug Candidates via Enantioselective Tsuji Allylation and Organocatalytic Aza-Ene-Type Domino Reactions

This work aims at exploiting both the enantioselective Tsuji allylation of allyl carbonate 6 and an organocatalytic aza-ene-type domino reaction between enal 3a and β-enaminone 4a to develop a straightforward access to all of the four possible stereoisomers of a donepezil-like 1,4-dihydropyridine 1a...

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Bibliographic Details
Published in:Journal of organic chemistry 2018-09, Vol.83 (17), p.10231-10240
Main Authors: Ţînţaş, Mihaela-Liliana, Azzouz, Rabah, Peauger, Ludovic, Gembus, Vincent, Petit, Emilie, Bailly, Laetitia, Papamicaël, Cyril, Levacher, Vincent
Format: Article
Language:English
Subjects:
Chemical Sciences
Organic chemistry
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Summary:This work aims at exploiting both the enantioselective Tsuji allylation of allyl carbonate 6 and an organocatalytic aza-ene-type domino reaction between enal 3a and β-enaminone 4a to develop a straightforward access to all of the four possible stereoisomers of a donepezil-like 1,4-dihydropyridine 1a (er up to 99.5:0.5; overall yield up 64%), an anti-Alzheimer’s prodrug candidate. This strategy was extended to the preparation of other enantioenriched 1,4-dihydropyridines 1b–i (eight examples), highlighting its potential in the development of these chiral AChE inhibitors.
ISSN:0022-3263
1520-6904
DOI:10.1021/acs.joc.8b01442